Praziquantel (PZQ), sold under the brandname Biltricide among others, is a medication used to treat a number of types of parasitic worm infections in mammals, birds, amphibians, reptiles, and fish. In humans specifically, it is used to treat

schistosomiasis Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever, is a disease caused by parasitic flatworms called schistosomes. The urinary tract or the intestines may be infected. Symptoms include abdominal pain, diarrhea, bloody ...

, clonorchiasis, opisthorchiasis, tapeworm infections, cysticercosis,

echinococcosis Echinococcosis is a parasitic disease of tapeworms of the ''Echinococcus'' type. The two main types of the disease are ''cystic echinococcosis'' and '' alveolar echinococcosis''. Less common forms include ''polycystic echinococcosis'' and ''un ...

, paragonimiasis, fasciolopsiasis, and fasciolosis. It should not be used for worm infections of the eye. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. Side effects in humans may include poor coordination, abdominal pain, vomiting, headache, and allergic reactions. While it may be used during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

, it is not recommended for use during

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...

. Praziquantel is in the

anthelmintic Anthelmintics or antihelminthics are a group of antiparasitic, antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the h ...

class of medications. It works partly by affecting the function of the worm's sucker. Praziquantel was approved for medical use in the United States in 1982. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

Medical uses

Praziquantel is used to treat diseases caused by infection with several types of internal/gastrointestinal, and external parasites, including: * Hydatid disease caused by infection of various organs with larval stages of tapeworms of the genus ''

Echinococcus ''Echinococcus'' is a genus within Cestoda, a parasitic class of the platyhelminthes phylum (colloquially known as flatworms). Human echinococcosis is an infectious disease caused by the following species: E. granulosus, E. multilocularis, ...

'' * Cysticercosis caused by infection of the brain and/or muscles with the eggs and larvae of the pork tapeworm ''

Taenia solium ''Taenia solium'', the pork tapeworm, belongs to the cyclophyllid cestode family Taeniidae. It is found throughout the world and is most common in countries where pork is eaten. It is a tapeworm that uses humans as its definitive host and p ...

'' (though it has been judged less effective than

albendazole Albendazole (also known as albendazolum) is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infectio ...

in treatment of neurocysticercosis) * In dogs and cats, whose gastrointestinal tracts are infected with the tapeworms '' Dipylidium caninum'' or '' Taenia taeniaeformis'', respectively; praziquantel is also often used in fixed combination with pyrantel embonate against the roundworms ( ascarids): '' Toxocara cati'' and ''

Toxascaris leonina ''Toxascaris leonina'' is a common parasitic roundworm found in dogs, cats, foxes, and related host species. ''T. leonina'' is an ascarid nematode, a worldwide distributed helminth parasite which is in a division of eukaryotic parasites that, ...

''. Praziquantel is also effective against ''

Echinococcus multilocularis ''Echinococcus multilocularis'' is a small cyclophyllid tapeworm found extensively in the northern hemisphere. ''E. multilocularis,'' along with other members of the ''Echinococcus'' genus (especially '' E. granulosus''), produce diseases known ...

''. *

Schistosomiasis Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever, is a disease caused by parasitic flatworms called schistosomes. The urinary tract or the intestines may be infected. Symptoms include abdominal pain, diarrhea, bloody ...

caused by

trematodes Trematoda is a class of flatworms known as flukes. They are obligate internal parasites with a complex life cycle requiring at least two hosts. The intermediate host, in which asexual reproduction occurs, is usually a snail. The definitive ...

of the genus '' Schistosoma'': As of 2005, praziquantel is the primary treatment for human

, for which it is usually effective in a single dose. * Clonorchiasis brought on by the Chinese liver fluke ''

Clonorchis sinensis ''Clonorchis sinensis'', the Chinese liver fluke, is a liver fluke belonging to the class Trematoda, phylum Platyhelminthes. It infects fish-eating mammals, including humans. In humans, it infects the common bile duct and gall bladder, feeding ...

'' * Paragonimiasis caused by infection with lung flukes, mostly of the species ''

Paragonimus westermani ''Paragonimus westermani'' (Japanese lung fluke or oriental lung fluke) is the most common species of lung fluke that infects humans, causing paragonimiasis. Human infections are most common in eastern Asia and in South America. Paragonimiasis ma ...

'' * Fasciolopsiasis caused by intestinal fluke '' Fasciolopsis buski''

Side effects

The majority of side effects develop due to the release of the contents of the parasites as they are killed and the consequent host immune reaction. The heavier the parasite burden, the heavier and more frequent the side effects normally are. * Central nervous system (CNS): Frequently occurring side effects are

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a resul ...

, and malaise.

Drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asle ...

, somnolence,

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, and

vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties ...

have also been seen. Almost all patients with cerebral cysticercosis experience CNS side effects related to the cell-death of the parasites (headache, worsening of pre-existing neurological problems,

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

, arachnoiditis, and meningism). These side effects may be life-threatening and can be reduced by coadministration of

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are in ...

s. All patients with cerebral cysticercosis are strongly recommended to be hospitalized during treatment. * Gastrointestinal tract: About 90% of all patients have abdominal pain or cramps with or without nausea and vomiting.

Diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin ...

may develop and may be severe with colic. Sweating, fever, and sometimes bloody stools may occur together with diarrhea. * Liver: Asymptomatic and transient increases of liver enzymes ( AST and ALT) are noted frequently (up to 27%). No case of symptomatic liver damage has been seen so far. * Sensitivity reactions:

Urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...

pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

and

eosinophilia Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds . Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 x 109/ L (i.e. 1,500/ μL). The hypereosinophilic synd ...

in white blood cell counts * Other locations/body as a whole: Lower back pain, myalgia, arthralgia, fever, sweating, various cardiac arrhythmias, and

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

Pregnancy

The WHO states praziquantel is safe during pregnancy. Animal studies have failed to reveal evidence of fetal harm. Praziquantel is effective in reducing schistosomiasis during pregnancy. Another trial found that treatment with praziquantel did not increase the rates of low birthweight, fetal death, or congenital anomalies.

Drug interactions

The antibiotic

rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used ...

decreases plasma concentrations of praziquantel.

Carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medi ...

and

phenytoin Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intr ...

are reported to reduce the bioavailability of praziquantel.

Chloroquine Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...

also reduces its bioavailability. The drug cimetidine heightens praziquantel bioavailability.

Mechanism of action

The drug's mode of action is not exactly known at present, but experimental evidence indicates praziquantel increases the permeability of the membranes of schistosome cells towards calcium ions. The drug thereby induces contraction of the parasites' muscle, resulting in paralysis in the contracted state. The dying parasites are dislodged from their site of action in the host organism and may enter systemic circulation or may be destroyed by host immune reaction (

phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis i ...

). Additional mechanisms including focal disintegrations and disturbances of oviposition (laying of eggs) are seen in other types of sensitive parasites. Another hypothesis regarding the mechanism of action is that it interferes with

adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside buildin ...

uptake in worms. This effect may have therapeutical relevance given that the schistosome, as the ''Taenia'' and the ''

'' (other praziquantel-sensitive parasites), is unable to synthesize

purine Purine is a heterocyclic aromatic organic compound that consists of two rings ( pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purin ...

s, such as adenosine, ''de novo''. Bayer's Animal Health Division website states, "Praziquantel is active against cestodes (tapeworms). Praziquantel is absorbed, metabolized in the liver, and excreted in the bile. Upon entering the digestive tract from the bile, cestocidal activity is exhibited. Following exposure to praziquantel, the tapeworm loses its ability to resist digestion by the mammalian host. Because of this, whole tapeworms, including the scolices (plural of "scolex"), are very rarely passed after administration of praziquantel. In many instances, only disintegrated and partially digested pieces of tapeworms will be seen in the stool. The majority of tapeworms are digested and are not found in the feces." Praziquantel is administered as a

racemate In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

, but only the (''R'')-

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

is biologically active; the enantiomers may be separated using a resolution of an

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent su ...

obtained from praziquantel.

Pharmacokinetics

Praziquantel is well absorbed (about 80%) from the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans a ...

. However, due to extensive first-pass metabolism, only a relatively small amount enters systemic circulation. Praziquantel has a

serum Serum may refer to: *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid * Truth serum, a drug that is likely to mak ...

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...

of 0.8 to 1.5 hours in adults with normal renal and liver function.

Metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

s have a half-life of 4 to 5 hours. In patients with significantly impaired liver function ( Child-Pugh score B and C), the serum half-life is increased to 3 to 8 hours. Praziquantel and its metabolites are mainly excreted renally; within 24 h after a single oral dose, 70 to 80% is found in urine, but less than 0.1% as the unchanged drug. Praziquantel is metabolized through the

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

pathway via

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules ( xenobiotics), such as toxins or drugs, so that they can be removed from t ...

. Agents that induce or inhibit CYP3A4 such as

, rifampin, and azole antifungals will affect the metabolism of praziquantel. Praziquantel has a particularly dramatic effect on patients with

. Studies of those treated have shown that within six months of receiving a dose of praziquantel, up to 90% of the damage done to internal organs due to schistosomiasis infection can be reversed.

History

Praziquantel was developed in the laboratories for parasitological research of

Bayer AG Bayer AG (, commonly pronounced ; ) is a German multinational pharmaceutical and biotechnology company and one of the largest pharmaceutical companies in the world. Headquartered in Leverkusen, Bayer's areas of business include pharmaceutica ...

and

Merck KGaA The Merck Group, branded and commonly known as Merck, is a German multinational science and technology company headquartered in Darmstadt, with about 60,000 employees and present in 66 countries. The group includes around 250 companies; the ma ...

in Germany (Elberfeld and Darmstadt) in the mid-1970s.

Society and culture

Brand names

* Biltricide (

Bayer Bayer AG (, commonly pronounced ; ) is a German multinational pharmaceutical and biotechnology company and one of the largest pharmaceutical companies in the world. Headquartered in Leverkusen, Bayer's areas of business include pharmaceutica ...

) Tablets (for human use) * Cesol ( Merck) Tablets * Cestoved ( Vedco) both tablets and injectable for veterinary use * Cysticide (Merck) Tablets * Distocide (Shin Poong Pharm. Co., Ltd.) tablet (for human use) * Distoside ( Chandra Bhagat Pharma Pvt Ltd) tablet (for human use) * Droncit (Bayer) for veterinary use * Drontal (combination with pyrantel pamoate) (Bayer) for veterinary use * D-Worm (Farnum) for veterinary use; note that D-Worm also makes roundworm medicine containing

piperidine Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic compound, heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless ...

which is not effective against tapeworms. * Fish Tapes (Thomas Labs) for aquarium use * Interceptor Plus chewable tablets (combination with milbemycin) (

Elanco Elanco Animal Health Incorporated is an American pharmaceutical company which produces medicines and vaccinations for pets and livestock. Until 2019, the company was a subsidiary of Eli Lilly and Company, before being divested. It is the th ...

) for veterinary use. Note regular Interceptor only has milbemycin and does not contain praziquantel. * Kaicide (Taiwan) * Milbemax (combination with

milbemycin oxime Milbemycin oxime, sold under the brand name Interceptor among others, is a veterinary medication from the group of milbemycins, used as a broad spectrum antiparasitic. It is active against worms (anthelmintic) and mites (miticide). Mechanism of ...

) (

Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-loc ...

) for veterinary use * Popantel ( Jurox) * PraziPro ( Hikari) for aquarium use * Praz-Tastic (NFP/ National Fish Pharmaceuticals) for aquarium use * Pure Prazi ( COTS Koi/Children of the Sun Koi) for aquarium use * PraziPure (J.K.O., Inc. d/b/a Kodama Koi Farm & Kodama Koi Garden; licensed by COTS Koi) for aquarium use * Profender (combination with emodepside) (Bayer) for veterinary use * Tape Worm Tabs (

Trade Winds The trade winds or easterlies are the permanent east-to-west prevailing winds that flow in the Earth's equatorial region. The trade winds blow mainly from the northeast in the Northern Hemisphere and from the southeast in the Southern Hemisp ...

) for veterinary use * Zentozide (

Berich Berich ( fa, بريچ, also Romanized as Berīch; also known as Behrīj) is a village in Soghan Rural District, Soghan District, Arzuiyeh County Arzuiyeh County ( fa, شهرستان ارزوئیه) is in Kerman province, Iran. The capital of ...

(Thailand) Co)

Regulatory approval

Praziquantel is on the World Health Organization's List of Essential Medicines. Praziquantel is not licensed for use in humans in the UK, but it can be imported when necessary on a named-patient basis. It is available in the UK as a veterinary anthelmintic. Praziquantel is FDA approved in the US for the treatment of schistosomiasis and liver flukes, although it is effective in other infections.

Veterinary medicine

Salmon poisoning disease ''Neorickettsia helminthoeca'' is a bacterium in the ''Neorickettsia'' genus that causes Salmon poisoning disease. Salmon poisoning disease Salmon poisoning disease (SPD) is a fatal disease of dogs and other canids caused by a rickettsial bacte ...

* ''

Diplozoon paradoxum ''Diplozoon paradoxum'' is a flatworm (platyhelminth) from the class Monogenea. It is found in freshwater fishes in Asia and Europe and known for its complete monogamy. This parasite is commonly found on the gills of European cyprinid fishes. It ...

'' and other Trematoda infections of many fish species It may cause problems in dogs with ''MDR''1 mutations.

References

External links

* * {{portal bar, Medicine Anthelmintics Antiparasitic agents Carboxamides Merck brands Lactams Wikipedia medicine articles ready to translate Veterinary drugs World Health Organization essential medicines Nitrogen heterocycles Heterocyclic compounds with 3 rings Cyclohexyl compounds